Physicochemical properties and oral bioavailability of amorphous atorvastatin hemi-calcium using spray-drying and SAS process

Jeong Soo Kim, Min Soo Kim, Hee Jun Park, Shun Ji Jin, Sibeum Lee, Sung Joo Hwang

Research output: Contribution to journalArticle

103 Citations (Scopus)

Abstract

The objective of the study was to prepare amorphous atorvastatin hemi-calcium using spray-drying and supercritical antisolvent (SAS) process and evaluate its physicochemical properties and oral bioavailability. Atorvastatin hemi-calcium trihydrate was transformed to anhydrous amorphous form by spray-drying and SAS process. With the SAS process, the mean particle size and the specific surface area of amorphous atorvastatin were drastically changed to 68.7 ± 15.8 nm, 120.35 ± 1.40 m 2 /g and 95.7 ± 12.2 nm, 79.78 ± 0.93 m 2 /g from an acetone solution and a tetrahydrofuran solution, respectively and appeared to be associated with better performance in apparent solubility, dissolution and pharmacokinetic studies, compared with unprocessed crystalline atorvastatin. Oral AUC 0-8 h values in SD rats for crystalline and amorphous atorvastatin were as follow: 1121.4 ± 212.0 ng h/mL for crystalline atorvastatin, 3249.5 ± 406.4 ng h/mL and 3016.1 ± 200.3 ng h/mL for amorphous atorvastatin from an acetone solution and a tetrahydrofuran solution with SAS process, 2227.8 ± 274.5 and 2099.9 ± 339.2 ng h/mL for amorphous atorvastatin from acetone and tetrahydrofuran with spray-drying. The AUCs of all amorphous atorvastatin significantly increased (P < 0.05) compared with crystalline atorvastatin, suggesting that the enhanced bioavailability was attributed to amorphous nature and particle size reduction. In addition, the SAS process exhibits better bioavailability than spray-drying because of particle size reduction with narrow particle size distribution. It was concluded that physicochemical properties and bioavailability of crystalline atorvastatin could be improved by physical modification such as particle size reduction and generation of amorphous state using spray-drying and SAS process. Further, SAS process was a powerful methodology for improving the physicochemical properties and bioavailability of atorvastatin.

Original languageEnglish
Pages (from-to)211-219
Number of pages9
JournalInternational Journal of Pharmaceutics
Volume359
Issue number1-2
DOIs
Publication statusPublished - 2008 Jul 9

Fingerprint

Biological Availability
Particle Size
Acetone
Area Under Curve
Atorvastatin Calcium
Solubility
Pharmacokinetics

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

Cite this

Kim, Jeong Soo ; Kim, Min Soo ; Park, Hee Jun ; Jin, Shun Ji ; Lee, Sibeum ; Hwang, Sung Joo. / Physicochemical properties and oral bioavailability of amorphous atorvastatin hemi-calcium using spray-drying and SAS process. In: International Journal of Pharmaceutics. 2008 ; Vol. 359, No. 1-2. pp. 211-219.
@article{c26dd9e8e44d4b0dac3e42683b8162ce,
title = "Physicochemical properties and oral bioavailability of amorphous atorvastatin hemi-calcium using spray-drying and SAS process",
abstract = "The objective of the study was to prepare amorphous atorvastatin hemi-calcium using spray-drying and supercritical antisolvent (SAS) process and evaluate its physicochemical properties and oral bioavailability. Atorvastatin hemi-calcium trihydrate was transformed to anhydrous amorphous form by spray-drying and SAS process. With the SAS process, the mean particle size and the specific surface area of amorphous atorvastatin were drastically changed to 68.7 ± 15.8 nm, 120.35 ± 1.40 m 2 /g and 95.7 ± 12.2 nm, 79.78 ± 0.93 m 2 /g from an acetone solution and a tetrahydrofuran solution, respectively and appeared to be associated with better performance in apparent solubility, dissolution and pharmacokinetic studies, compared with unprocessed crystalline atorvastatin. Oral AUC 0-8 h values in SD rats for crystalline and amorphous atorvastatin were as follow: 1121.4 ± 212.0 ng h/mL for crystalline atorvastatin, 3249.5 ± 406.4 ng h/mL and 3016.1 ± 200.3 ng h/mL for amorphous atorvastatin from an acetone solution and a tetrahydrofuran solution with SAS process, 2227.8 ± 274.5 and 2099.9 ± 339.2 ng h/mL for amorphous atorvastatin from acetone and tetrahydrofuran with spray-drying. The AUCs of all amorphous atorvastatin significantly increased (P < 0.05) compared with crystalline atorvastatin, suggesting that the enhanced bioavailability was attributed to amorphous nature and particle size reduction. In addition, the SAS process exhibits better bioavailability than spray-drying because of particle size reduction with narrow particle size distribution. It was concluded that physicochemical properties and bioavailability of crystalline atorvastatin could be improved by physical modification such as particle size reduction and generation of amorphous state using spray-drying and SAS process. Further, SAS process was a powerful methodology for improving the physicochemical properties and bioavailability of atorvastatin.",
author = "Kim, {Jeong Soo} and Kim, {Min Soo} and Park, {Hee Jun} and Jin, {Shun Ji} and Sibeum Lee and Hwang, {Sung Joo}",
year = "2008",
month = "7",
day = "9",
doi = "10.1016/j.ijpharm.2008.04.006",
language = "English",
volume = "359",
pages = "211--219",
journal = "International Journal of Pharmaceutics",
issn = "0378-5173",
publisher = "Elsevier",
number = "1-2",

}

Physicochemical properties and oral bioavailability of amorphous atorvastatin hemi-calcium using spray-drying and SAS process. / Kim, Jeong Soo; Kim, Min Soo; Park, Hee Jun; Jin, Shun Ji; Lee, Sibeum; Hwang, Sung Joo.

In: International Journal of Pharmaceutics, Vol. 359, No. 1-2, 09.07.2008, p. 211-219.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Physicochemical properties and oral bioavailability of amorphous atorvastatin hemi-calcium using spray-drying and SAS process

AU - Kim, Jeong Soo

AU - Kim, Min Soo

AU - Park, Hee Jun

AU - Jin, Shun Ji

AU - Lee, Sibeum

AU - Hwang, Sung Joo

PY - 2008/7/9

Y1 - 2008/7/9

N2 - The objective of the study was to prepare amorphous atorvastatin hemi-calcium using spray-drying and supercritical antisolvent (SAS) process and evaluate its physicochemical properties and oral bioavailability. Atorvastatin hemi-calcium trihydrate was transformed to anhydrous amorphous form by spray-drying and SAS process. With the SAS process, the mean particle size and the specific surface area of amorphous atorvastatin were drastically changed to 68.7 ± 15.8 nm, 120.35 ± 1.40 m 2 /g and 95.7 ± 12.2 nm, 79.78 ± 0.93 m 2 /g from an acetone solution and a tetrahydrofuran solution, respectively and appeared to be associated with better performance in apparent solubility, dissolution and pharmacokinetic studies, compared with unprocessed crystalline atorvastatin. Oral AUC 0-8 h values in SD rats for crystalline and amorphous atorvastatin were as follow: 1121.4 ± 212.0 ng h/mL for crystalline atorvastatin, 3249.5 ± 406.4 ng h/mL and 3016.1 ± 200.3 ng h/mL for amorphous atorvastatin from an acetone solution and a tetrahydrofuran solution with SAS process, 2227.8 ± 274.5 and 2099.9 ± 339.2 ng h/mL for amorphous atorvastatin from acetone and tetrahydrofuran with spray-drying. The AUCs of all amorphous atorvastatin significantly increased (P < 0.05) compared with crystalline atorvastatin, suggesting that the enhanced bioavailability was attributed to amorphous nature and particle size reduction. In addition, the SAS process exhibits better bioavailability than spray-drying because of particle size reduction with narrow particle size distribution. It was concluded that physicochemical properties and bioavailability of crystalline atorvastatin could be improved by physical modification such as particle size reduction and generation of amorphous state using spray-drying and SAS process. Further, SAS process was a powerful methodology for improving the physicochemical properties and bioavailability of atorvastatin.

AB - The objective of the study was to prepare amorphous atorvastatin hemi-calcium using spray-drying and supercritical antisolvent (SAS) process and evaluate its physicochemical properties and oral bioavailability. Atorvastatin hemi-calcium trihydrate was transformed to anhydrous amorphous form by spray-drying and SAS process. With the SAS process, the mean particle size and the specific surface area of amorphous atorvastatin were drastically changed to 68.7 ± 15.8 nm, 120.35 ± 1.40 m 2 /g and 95.7 ± 12.2 nm, 79.78 ± 0.93 m 2 /g from an acetone solution and a tetrahydrofuran solution, respectively and appeared to be associated with better performance in apparent solubility, dissolution and pharmacokinetic studies, compared with unprocessed crystalline atorvastatin. Oral AUC 0-8 h values in SD rats for crystalline and amorphous atorvastatin were as follow: 1121.4 ± 212.0 ng h/mL for crystalline atorvastatin, 3249.5 ± 406.4 ng h/mL and 3016.1 ± 200.3 ng h/mL for amorphous atorvastatin from an acetone solution and a tetrahydrofuran solution with SAS process, 2227.8 ± 274.5 and 2099.9 ± 339.2 ng h/mL for amorphous atorvastatin from acetone and tetrahydrofuran with spray-drying. The AUCs of all amorphous atorvastatin significantly increased (P < 0.05) compared with crystalline atorvastatin, suggesting that the enhanced bioavailability was attributed to amorphous nature and particle size reduction. In addition, the SAS process exhibits better bioavailability than spray-drying because of particle size reduction with narrow particle size distribution. It was concluded that physicochemical properties and bioavailability of crystalline atorvastatin could be improved by physical modification such as particle size reduction and generation of amorphous state using spray-drying and SAS process. Further, SAS process was a powerful methodology for improving the physicochemical properties and bioavailability of atorvastatin.

UR - http://www.scopus.com/inward/record.url?scp=44749087764&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=44749087764&partnerID=8YFLogxK

U2 - 10.1016/j.ijpharm.2008.04.006

DO - 10.1016/j.ijpharm.2008.04.006

M3 - Article

VL - 359

SP - 211

EP - 219

JO - International Journal of Pharmaceutics

JF - International Journal of Pharmaceutics

SN - 0378-5173

IS - 1-2

ER -